基于“蛇足石杉内生真菌生物转化”的lycodine型生物碱类似物制备及胆碱酯酶活性评价

微生物转化是天然产物结构修饰的有效手段。植物内生真菌是一种新型微生物资源，内生真菌与宿主间相互关系、及其次级代谢产物的研究已取得了诸多喜人的结果。然而，内生真菌在天然产物生物转化领域的应用尚处于起步阶段，其应用前景有待进一步认识与挖掘。在前期的研究中，我们发现，蛇足石杉内生真菌对宿主化学成分石杉碱甲的生物转化具有转化产率高、反应类型新颖等特点。提示我们，此类生物转化方式是开展植物天然产物结构修饰的又一有效手段。同时，也引发我们思考，内生真菌在宿主化学成分的生物转化方面可能具有独特的优势。. 本项目拟在前期研究的基础上，利用蛇足石杉内生真菌对宿主化学成分的生物转化作用，开展石松定碱类乙酰胆碱酯酶（AChE）抑制成分（石杉碱甲、石杉碱乙和石松定碱）的结构修饰，以寻求活性更好、选择性更高的AChE抑制剂，并探索此类生物转化作用的特点与规律。

Microbial transformation has been proved to be an effective method for the structure modification of natural products. The past few decades have witnessed lots of encouraging achievement in the study of the secondary metabolites of fungal endopytes and its interaction with their hosts. However, studies on the biotransformation of natural products by fungal endophyte are still limited and waiting for further exploration. In our previous studies on the biotransformation of huperzine a (a constituent of Huperzia serrata) by an fungal endophyte derived from Huperzia serrata, a transformation process with high product yields and novel types of catalysis was observed, implying that biotransformation of host-associated natural products by fungal endophytes of the host may serve as an alternative way for the structural modification of plant-derived natural products. It also prompts us to infer that fungal endophyts may possess unique advantages in the biotransformation of host constituents over other microorganisms.. Based on the discovery and speculation of our previous studies, fungal endophytes of Huperzia serrata are to be employed for the structure modification of lycodine-type acetylcholinesterase (AChE) inhibitors including huperzine a, huperzine b, and lycodine, three alkaloid constituents of Huperzia serrata sharing the same lycodine-type skeleton. Results of our study may provide lycodine-type AChE inhibitors with more potency and/or higher selectivity, and may also unveil the features and underlying laws of such kind of biotransformation.